NCT01441856

Brief Summary

The added value of the laparoscopic hemihepatectomy compared to the open hemihepatectomy has never been studied in a randomized controlled setting. Therefore, the multicenter international ORANGE II PLUS - trial has been constructed and will provide evidence on the merits of laparoscopic versus open hemihepatectomy in terms of time to functional recovery, hospital length of stay, intraoperative blood loss, operation time, resection margin, time to adjuvant chemotherapy initiation, readmission percentage, (liver-specific) morbidity, quality of life, body image, reasons for delay of discharge after functional recovery, long term incidence of incisional hernias, hospital and societal costs during one year and overall five-year survival.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
350

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Oct 2013

Longer than P75 for not_applicable

Geographic Reach
6 countries

16 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 27, 2011

Completed
5 months until next milestone

First Posted

Study publicly available on registry

September 28, 2011

Completed
2 years until next milestone

Study Start

First participant enrolled

October 1, 2013

Completed
6.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 4, 2019

Completed
4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 4, 2023

Completed
Last Updated

May 18, 2025

Status Verified

May 1, 2025

Enrollment Period

6.2 years

First QC Date

April 27, 2011

Last Update Submit

May 16, 2025

Conditions

Liver Lesions Requiring Hemihepatectomy

Keywords

OpenLaparoscopicHemihepatectomyHepatectomyEnhanced Recovery After SurgeryFunctional recovery

Outcome Measures

Primary Outcomes (1)

  • Time to functional recovery

    Time until a patient is functionally recovered

    expected average of 4-10 days

Secondary Outcomes (15)

  • Length of hospital stay

    30 days

  • Readmission percentage

    1 year

  • Total morbidity

    1 year

  • Composite endpoint of liver specific morbidity

    1 year

  • Long term incidence of incisional hernia

    1 year

  • +10 more secondary outcomes

Study Arms (3)

Open or Laparocopic Left

ACTIVE COMPARATOR

Open or Laparoscopic left hemihepatectomy

Procedure: Open or Laparoscopic left hemihepatectomy

Open or Laparoscopic Right

ACTIVE COMPARATOR

Open or Laparoscopic right hemihepatectomy

Procedure: Open or Laparoscopic right hemihepatectomy

Prospective registry

ACTIVE COMPARATOR

Prospective registry of patients that cannot be randomized (both open and laparoscopic left + right hemihepatectomy)

Procedure: Open or Laparoscopic left hemihepatectomyProcedure: Open or Laparoscopic right hemihepatectomy

Interventions

Open or Laparoscopic left hemihepatectomyPROCEDURE

Patients in this arm will undergo a left hemihepatectomy within an Enhanced Recovery After Surgery Program.

Open or Laparocopic LeftProspective registry
Open or Laparoscopic right hemihepatectomyPROCEDURE

Patients in this arm will undergo a right hemihepatectomy within an Enhanced Recovery After Surgery Program.

Open or Laparoscopic RightProspective registry

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients requiring open or laparoscopic left / right hemihepatectomy, with or without the need for one additional hepatic wedge resection or metastasectomy, for accepted indications.
  • Able to understand the nature of the study and what will be required of them.
  • Men and non-pregnant, non-lactating women age 18 years and older.
  • BMI between 18-35.
  • Patients with ASA I-II-III.

You may not qualify if:

  • Inability to give written informed consent.
  • Patients undergoing liver resection other than left or right hemihepatectomy, with or without the need for one additional hepatic wedge resection or metastasectomy.
  • Patients with hepatic lesion(s), that are located with insufficient margin from vascular or biliary structures to be operated laparoscopically.
  • Patients with ASA IV-V.
  • Repeat hepatectomy.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (16)

Erasmus Hospital

Brussels, Belgium

Location

Ghent University Hospital

Ghent, Belgium

Location

Jessa Hospital

Hasselt, Belgium

Location

General Hospital Groeninge

Kortrijk, Belgium

Location

University Hospital Aachen

Aachen, Germany

Location

San Raffaele Hospital

Milan, Italy

Location

Academic Medical Center

Amsterdam, Netherlands

Location

Maastricht University Medical Center+

Maastricht, Netherlands

Location

University Hospital Oslo

Oslo, Norway

Location

Aintree University Hospital

Aintree, United Kingdom

Location

Queen Elizabeth Hospital

Birmingham, United Kingdom

Location

King's College Hospital

London, United Kingdom

Location

Freeman Hospital

Newcastle, United Kingdom

Location

Oxford University Hospitals

Oxford, United Kingdom

Location

Derriford Hospital

Plymouth, United Kingdom

Location

University Hospital Southampton

Southampton, United Kingdom

Location

Related Publications (3)

  • Olij B, Pilz da Cunha G, Kimman M, Ratti F, Abu Hilal M, Troisi RI, Sutcliffe RP, Besselink MG, Aroori S, Menon KV, Edwin B, D'Hondt M, Lucidi V, Ulmer TF, Diaz-Nieto R, Soonawalla Z, White S, Sergeant G, Coolsen MME, Kuemmerli C, Scuderi V, Berrevoet F, Vanlander A, Marudanayagam R, Tanis PJ, Dewulf MJL, Fichtinger RS, Eminton ZB, Neumann UP, Brandts L, Pugh SA, Fretland AA, Primrose JN, van Dam RM; ORANGE II PLUS Collaborative. Healthcare Utilization, Costs, and Cost-Effectiveness of Patients Undergoing Laparoscopic and Open Hemihepatectomy: A Secondary Analysis of the ORANGE II PLUS Randomized Controlled, Phase 3, Superiority Trial. Ann Surg Oncol. 2025 Dec 12. doi: 10.1245/s10434-025-18779-4. Online ahead of print.

    PMID: 41385067DERIVED

  • Olij B, Fichtinger RS, Aldrighetti LA, Abu Hilal M, Troisi RI, Sutcliffe RP, Besselink MG, Aroori S, Menon KV, Edwin B, D'Hondt M, Lucidi V, Ulmer TF, Diaz-Nieto R, Soonawalla Z, White S, Sergeant G, Ratti F, Kuemmerli C, Scuderi V, Berrevoet F, Vanlander A, Marudanayagam R, Tanis PJ, Dewulf MJL, Eminton ZB, Neumann UP, Brandts L, Pugh SA, Fretland AA, Kimman ML, Primrose JN, van Dam RM; ORANGE II PLUS Collaborative. Health-related quality of life in patients undergoing laparoscopic versus open hemihepatectomy: a secondary analysis of the ORANGE II PLUS randomised controlled, phase 3, superiority trial. Lancet Reg Health Eur. 2025 May 19;54:101311. doi: 10.1016/j.lanepe.2025.101311. eCollection 2025 Jul.

    PMID: 40491830DERIVED

  • Fichtinger RS, Aldrighetti LA, Abu Hilal M, Troisi RI, Sutcliffe RP, Besselink MG, Aroori S, Menon KV, Edwin B, D'Hondt M, Lucidi V, Ulmer TF, Diaz-Nieto R, Soonawalla Z, White S, Sergeant G, Olij B, Ratti F, Kuemmerli C, Scuderi V, Berrevoet F, Vanlander A, Marudanayagam R, Tanis P, Dewulf MJL, Dejong CHC, Eminton Z, Kimman ML, Brandts L, Neumann UP, Fretland AA, Pugh SA, van Breukelen GJP, Primrose JN, van Dam RM; ORANGE II PLUS Collaborative. Laparoscopic Versus Open Hemihepatectomy: The ORANGE II PLUS Multicenter Randomized Controlled Trial. J Clin Oncol. 2024 May 20;42(15):1799-1809. doi: 10.1200/JCO.23.01019. Epub 2024 Apr 19.

    PMID: 38640453DERIVED

Study Officials

  • R.M. van Dam, MD PhD

    Maastricht University Medical Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, CARE PROVIDER
Masking Details
The patient, surgical ward physician and surgical ward nurses are blinded up and until postoperative day 4.
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 27, 2011

First Posted

September 28, 2011

Study Start

October 1, 2013

Primary Completion

December 4, 2019

Study Completion

December 4, 2023

Last Updated

May 18, 2025

Record last verified: 2025-05

Data Sharing

IPD Sharing
Will not share

Locations

IT(1)NO(1)DE(1)NL(2)BE(4)GB(7)